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Human CD4CD103 Cutaneous Resident Memory T Cells Are Found in the Circulation of Healthy Individuals

Abstract

Tissue-resident memory T cells (T) persist locally in nonlymphoid tissues where they provide frontline defense against recurring insults. T at barrier surfaces express the markers CD103 and/or CD69, which function to retain them in epithelial tissues. In humans, neither the long-term migratory behavior of T nor their ability to reenter the circulation and potentially migrate to distant tissue sites has been investigated. Using tissue explant cultures, we found that CD4CD69CD103 T in human skin can down-regulate CD69 and exit the tissue. In addition, we identified a skin-tropic CD4CD69CD103 population in human lymph and blood that is transcriptionally, functionally, and clonally related to the CD4CD69CD103 T population in the skin. Using a skin xenograft model, we confirmed that a fraction of the human cutaneous CD4CD103 T population can reenter circulation and migrate to secondary human skin sites where they reassume a T phenotype. Thus, our data challenge current concepts regarding the strict tissue compartmentalization of CD4 T cell memory in humans.

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References
1.
Daley J, Thomay A, Connolly M, Reichner J, Albina J . Use of Ly6G-specific monoclonal antibody to deplete neutrophils in mice. J Leukoc Biol. 2007; 83(1):64-70. DOI: 10.1189/jlb.0407247. View

2.
Collins N, Jiang X, Zaid A, Macleod B, Li J, Park C . Skin CD4(+) memory T cells exhibit combined cluster-mediated retention and equilibration with the circulation. Nat Commun. 2016; 7:11514. PMC: 4866325. DOI: 10.1038/ncomms11514. View

3.
Dalessandri T, Crawford G, Hayes M, Castro Seoane R, Strid J . IL-13 from intraepithelial lymphocytes regulates tissue homeostasis and protects against carcinogenesis in the skin. Nat Commun. 2016; 7:12080. PMC: 4931319. DOI: 10.1038/ncomms12080. View

4.
Clark R, Chong B, Mirchandani N, Brinster N, Yamanaka K, Dowgiert R . The vast majority of CLA+ T cells are resident in normal skin. J Immunol. 2006; 176(7):4431-9. DOI: 10.4049/jimmunol.176.7.4431. View

5.
Mackay L, Wynne-Jones E, Freestone D, Pellicci D, Mielke L, Newman D . T-box Transcription Factors Combine with the Cytokines TGF-β and IL-15 to Control Tissue-Resident Memory T Cell Fate. Immunity. 2015; 43(6):1101-11. DOI: 10.1016/j.immuni.2015.11.008. View